Studies of sensory systems have contributed greatly to our understanding of normal brain function. The mouse olfactory system is a genetically tractable experimental model in which to study how sensory information is encoded by neuronal circuits. In this system, 1000 populations of olfactory sensory neurons project axons to the brain where they sort out by identity and form an array of glomeruli on the surface of the olfactory bulb. The spatial arrangement of glomeruli is thought to play a role in odor coding. We have recently discovered that the olfactory epithelium contains phenotypically distinct types of sensory neurons, and that these cell types play a role in mapping Class I and Class II odorant receptors to domains in the olfactory bulb. Generally, our hypothesis is that these sensory neuron types play a key role in organizing the glomerular array. The first two Specific Aims seek to define the identity of these cell types. The third Specific Aim seeks to examine the functional properties of one Class of these sensory neurons. These experiments will allow us to test and expand our cell-type hypothesis and to address the mechanisms by which neurons make specific connections in the olfactory system. PUBLIC HEALTH RELEVANCE: A fundamental question in neuroscience is how the brain processes information under normal and pathological conditions. The olfactory system is an excellent model in which to study how chemical information is represented in genetically tractable neuronal circuits. The experiments described in this proposal examine a new model for understanding how neurons in the peripheral olfactory system organize circuits in the olfactory bulb. We hope that the insights from this work will lead to a better understanding of how neurons self-assemble into functional neuronal networks.